Cancer

Question 1

Types of familial CRC (15% of CRC)

Answer 1

3-5% hnpcc,

Question 2

What does MSI-H indicate in CRC

Answer 2

25% associated with germline MMR mutations but 10-15% sporadic CRC also have. Therefore need to supplement with further test

Question 3

How is IHC used for CRC diagnosis

Answer 3

Staining looks for loss of MMR gene expression. Ie detects product +/- of MMR genes. Loss of MSH2 stain = absent IHC expression of MSH2 and MSh6, loss of MLH1= absent IHC of mlh1 and pms2. Isolated absence of msh6 or pms2 = mutation in that gene.

Question 4

What is MS-PCR used for in crc testing

Answer 4

Methylation status of mlh1 promotor . Often seen in sporadic non-lynch CRC and associated with BRAF V600E

Question 5

Why use BRAF screen in CRC?

Answer 5

Indicate if CRC sporadic before test MMR genes. Common in non-lynch MSI-H tumours.

Question 6

Discuss EPCAM mutation in lynch

Answer 6

Upstream of msh2. Deletion in EPCAM -> transcriptional read through and silencing of msh2

Question 7

Mutation seen in most FAP

Answer 7

75% have APC mutation

Question 8

Example of genotype-phenotype correlations in familial cancer syndromes

Answer 8

APC mutations- ass different types of FAP. Attenuated Fap, Gardner syndrome, diff ages of onset

Question 9

Techniques to test for APC abnormalities in FAP?

Answer 9

Sequencing detects 90% but mlpa useful to detect 10% with whole APC deletion

Question 10

Example of presumptions tic test available to minors

Answer 10

Fap

Question 11

Example of sumilar phenotype-different mechanism in CRC

Answer 11

Fap and map. APC and MutYH

Question 12

Inheritance pattern of APC

Answer 12

AD

Question 13

Inheritance pattern of MutYH

Answer 13

AR

Question 14

What is Her2?

Answer 14

Receptor TK encoded by EBBR2- amplified in 20-30% early stage breast cancer. Ass with more aggressive disease

Question 15

Side effects of herceptin

Answer 15

Increased risk heart diseas, 15% still relapse

Question 16

How is her2 amp measured

Answer 16

IHC 0-1: negative, 2: intermediate, 3: high. High will have fish test which measures amount per cell and will be either + or -

Question 17

How do PARPi work for breast cancer patients

Answer 17

Cause ds breaks to form. As brca positive cancer can’t repair, the cells apoptose

Question 18

% lung cancer that is nsclc

Answer 18

70%

Question 19

Which TKI used in nsclc . Which gene mutation is it effective against? Drawback?

Answer 19

Gefitinib. Directed against egfr mutation by blocking arp binding sites. Only works in 10% patients

Question 20

Importance of detecting kras mutation in nsclc

Answer 20

Mutually exclusive to egfr mutation- in 22% nsclc. Not sensitive to egfr TKI or adjuvent chemo

Question 21

What causes EML4-ALK fusion in lung adenocarcinoma

Answer 21

Para inv 2p21p23

Question 22

Drug used for eml4 - alk fusion in lung adenocarcinoma. Disadvantage for nice recommendation

Answer 22

Crizotinib. Nice won’t rec due to cost

Question 23

Challenges to stratified medicine

Answer 23

Standardisation of testing, linking to patient histories- privacy, large datasets req, need to understand mech not just ID a link, ethnicity role?, epigenetics effects?

Question 24

Why use stratified medicine

Answer 24

Current drugs only effective in 30-60%, cost reduction, prevent adverse reactions, right drugs at right time, smarter monitoring fits with 5yfv

Question 25

Aim of CRUK programme

Answer 25

Streamline and standardise genetic testing of tumour samples in nhs

Question 26

% CRC that is familial

Answer 26

15%